A fundamental question in neurobiology is how synaptic stimuli elicit long-term alterations in neuronal activity. Recent studies have demonstrated that neuronal stimulation can elicit rapid activation of several transcription factor genes. Accordingly, these factors, such as Zif268 and c-fos, are thought to play a key role in orchestrating alterations in gene expression underlying stimulus-induced neuronal plasticity. In previous studies, we have characterized extensively the regulation of zif268 in brain in several stimulation paradigms and found that it is markedly responsive to synaptic or pharmacologic stimuli. The goal of the proposed research outlined below is to move beyond these descriptive studies to define the mechanisms mediating neurotransmitter regulation to zif268. In particular, we plan to 1) use primary cortical cultures to study glutamate receptor regulation of zif268, and 2) examine the role of flanking DNA sequences in mediating neurotransmitter regulation of zif268. In the studies involving primary cortical cultures, I plan to integrate pharmacological and physiological approaches that I am largely familiar with. However, the studies examining regulatory DNA sequences will involve acquiring a wide range of advanced molecular biology techniques needed to study activity-dependent changes in gene expression in neuronal systems. To facilitate my professional growth in the area of molecular biology, I have arranged to consult on these projects with faculty members in the Departments of Neuroscience and Molecular Biology that have considerable expertise in this field.